Prostate cancer (PCa) is a malignant tumor that occurs in the prostate tissue of males, and is the result of abnormal growth of prostate acinar cells. The differentiation and growth of normal prostate epithelial cells as well as the development of prostate cancer all depend on androgen, which is mainly (about 80-90%) synthesized in the testes. Synthetic androgen binds to the androgen receptor (AR) after entering the cells, causing dissociation of heat shock protein (HSP) from AR, then the AR enters the nucleus and activates multiple downstream genes, including prostate-specific antigen (PSA). Early prostate cancer is sensitive to androgen, orchiectomy (castration) can thus significantly inhibit the development of prostate cancer. Although castration surgery is effective for a certain period of time, many patients undergo the transformation of androgen-dependent to androgen-independent during a period of time after castration. The prostate cancer of these patients develops into androgen independent prostate cancer (AIPC), and anti-androgen therapy is no longer effective to them. The occurrence of AIPC still has an important relationship with activation of the AR signaling pathway in PCa cells.
First-generation drugs, which aim at inhibiting AR activity, include Bicalutamide (or Casodex) and Flutamide. Second-generation AR antagonist drugs for AIPC therapy include MDV3100 and ARN-509. MDV3100 is the first second-generation non-steroidal AR antagonist drug in the world, and was approved by the U.S. Food and Drug Administration (FDA) at the end of August 2012. The affinity of MDV-3100 to AR is 5-8 times higher than that of bicalutamide. MDV-3100 can inhibit the growth of AIPC in mouse and human by inhibiting AR activity, and has no effect of promoting tumor cell growth.

International Patent Application Publication WO2014036897A1 discloses novel AR antagonists, comprising a compound of formula (I). The activity in vitro of this compound is slightly better than that of MDV-3100, and the hERG inhibition rate is further improved (IC50:24.83 μM). The inhibition half-lives of this compound toward five major subtypes of CYP450 are all greater than 50 μM. The in vivo exposure of this compound in rats is comparable to that of MDV-3100, and the in vivo exposure of this compound in dogs is more than six times that of MDV-3100 at the same dose and in the same solvent. The compound of formula (I) has only one chiral center. The chiral starting material is easy to obtain, and the synthesis difficulty is greatly reduced. In addition, the compound of formula (I) has no AR agonist activity at 3 μM and 10 μM, and the ratio of drug concentration in brain tissue to drug concentration in plasma in mice is much lower than that of MDV-3100 compound, and the possibility of epileptic side effects is smaller. Therefore, the compound of formula (I) has broad clinical prospects.

However, International Patent Application Publication WO2014036897A1 does not further investigate the crystal form of this compound. It is known to those skilled in the art that the crystal structure of a pharmaceutically active ingredient often affects the chemical stability of the drug. Different crystallization conditions and storage conditions can lead to changes in the crystal structure of the compound, and sometimes accompany production of other crystal forms. In general, an amorphous drug product does not have a regular crystal structure, and often has other defects, such as poor product stability, smaller particle size, difficult filtration, easy agglomeration, and poor liquidity. Therefore, it is necessary to improve the various properties of the above compound. There is a need to find a new crystal form with high purity and good chemical stability.